Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell.
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PMID:On the mechanism of ATP-induced shape changes in human erythrocyte membranes. II. The role of ATP. 19 4

The effect of thrombin on the phosphorylating activity of platelet membranes was compared to that of trypsin. Preincubation of non-32P phosphorylated platelet membranes with or without either of these two enzymes resulted in a considerable loss of membrane protein kinase activity which was most severe when trypsin was used. Protein kinase activity and endogenous protein acceptors decreased in parallel. 32P-phosphorylated membranes showed a slow but progressive loss of label which was accelerated by trypsin. Thrombin under these conditions prevented the loss of 32P-phosphate. These results are interpreted to indicate a thrombin-induced destruction of a phosphoprotein phosphatase. The protein kinase activity of phosphorylated platelet membranes using endogenous or exogenous protein substrates showed a significant reduction compared to non-phosphorylated membranes suggesting a deactivation of protein kinase by phosphorylation of platelet membranes. Neither thrombin nor trypsin caused a qualitative change in the membrane polypeptides accepting 32P-phosphate but resulted in quantitative alterations of their ability to become phosphorylated.
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PMID:Effect of thrombin on phosphorylation of platelet membrane proteins. 98 70

The present article deals with the stimulation of membrane PLA2 induced by activated protein kinase C (PKC), and the effect of a deficiency in cellular PKC activity in reducing in PLA2 activity. The mode of glucocorticoid (GC) inhibition action in regulation of PLA2 activity, by enhancement of protein dephosphorylation in general, and PLA2 in particular, is hypothesized and discussed. Indirect evidence strongly suggests that activated PKC enzyme is essential for the stimulation of membrane PLA2 activity induced by the Ca2+ ionophore A23187 and other agonists. Our hypothesis suggests that membrane-associated PKC directly phosphorylates PLA2 leading to its activation. Dephosphorylation of activated PLA2, possibly by a serine/threonine protein phosphatase reduces PLA2 activity. GC could induce membrane protein phosphatases which mediate their inhibitory action on PLA2 activity. This mode of action of GC is complementary to their effect in reducting in elevated [Ca2+]i, which is essential for full expression of PLA2 activity. Thus, GC exhibits multiple actions which specifically culminate in suppression of PLA2 and other phospholipases (PI-PLC and PLD) and generally in cellular inactivation (relaxation) and reduction of allergic and inflammatory responses.
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PMID:A novel mechanism of glucocorticosteroid (GC) action in suppression of phospholipase A2 (PLA2) activity stimulated by Ca2+ ionophore A23187: induction of protein phosphatases. 184 70

Human red cell cytosol acid phosphatase activity is supported by a main enzyme which can be extracted by DEAE and phosphocellulose chromatography. It uses pNPP as a substrate and is a protein phosphatase specific to phosphotyrosine. It dephosphorylates the tyrosine-phosphorylated cytosolic fragment of membrane protein 3. When taken together, these results suggest that the physiological role of red cell acid phosphatase is the FB3 phosphotyrosine dephosphorylation. Whatever it may be phosphotyrosine protein phosphatase activity is the first role of red cell acid phosphatase to be demonstrated.
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PMID:The human red cell acid phosphatase is a phosphotyrosine protein phosphatase which dephosphorylates the membrane protein band 3. 241 29

Purified alkaline phosphatase and plasma membranes from human liver were shown to dephosphorylate phosphohistones and plasma membrane phosphoproteins. The protein phosphatase activity of the liver plasma membranes was inhibited by levamisole, a specific inhibitor of alkaline phosphatase, and by phenyl phosphonate and orthovanadate, but was relatively insensitive to fluoride (50 mM). Endogenous membrane protein phosphatase activity was optimal at pH 8.0, compared to pH 7.8 for purified liver alkaline phosphatase. Plasma membranes also exhibited protein kinase activity using exogenous histone or endogenous membrane proteins (autophosphorylation) as substrates; this activity was cAMP-dependent. Autophosphorylation of plasma membrane proteins was apparently enhanced by phenyl phosphonate, levamisole, or orthovanadate. The dephosphorylation of phosphohistones by protein phosphatase 1 was not inhibited by levamisole but was inhibited by fluoride. Inhibition of endogenous protein phosphatase activity by orthovanadate during autophosphorylation of plasma membranes could be reversed by complexation of the inhibitor with (R)-(-)-epinephrine, and the dephosphorylation that followed was levamisole-sensitive. Neither plasma membranes nor purified liver alkaline phosphatase dephosphorylated glycogen phosphorylase a. These results suggest that the increased [32P]phosphate incorporation by endogenous protein kinases into the membrane proteins is due to inhibition of alkaline phosphatase and that the major protein phosphatase of these plasma membranes is alkaline phosphatase.
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PMID:Dephosphorylation of phosphoproteins of human liver plasma membranes by endogenous and purified liver alkaline phosphatases. 301 92

When sarcolemma membranes isolated from rat skeletal muscle were incubated with [gamma-32P]ATP, a membrane protein of apparent Mr 95,000 was rapidly phosphorylated, with the 32P content reaching a maximum within 2 s. On the basis of immunoprecipitation with anti-insulin-receptor antiserum, phosphoamino acid analysis and Mr, this protein probably represents the beta-subunit of the insulin receptor. Similarly, on incubation of the membrane with adenosine 5'-[gamma-[35S]thio] triphosphate the 95 kDa protein was thiophosphorylated, indicating thiophosphorylation of the beta-subunit of the insulin receptor on the basis of immunoprecipitation studies. The effect of insulin on the phosphorylation of this protein in the membrane was studied. Insulin induced a 20% decrease in the 32P labelling of the protein when the membranes were phosphorylated for 10 s. This insulin effect was dose-dependent, with half-maximal effect obtained at 2-3 nM-insulin. Addition of GTP, but not GDP or guanosine 5'-[beta, gamma-imido]triphosphate, enhanced the effect to 35% inhibition, with half-maximal effect of GTP obtained at 0.5 microM. GTP had no effect on the phosphorylation of the protein in the absence of insulin. Analysis of this insulin effect showed that insulin increased the rate of dephosphorylation of the 95 kDa protein in the membrane. In contrast, insulin had no effect on thiophosphorylation of the 95 kDa membrane protein after incubation with adenosine 5'-[gamma-[35S]thio]triphosphate. Since thiophosphorylated proteins are less sensitive to phosphatase action, these investigations suggest that insulin stimulated a protein phosphatase activity in a GTP-dependent manner. The possibility that GTP-regulatory proteins are involved in the action of insulin on the phosphorylation of the insulin receptor and other membrane proteins is discussed.
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PMID:Evidence that insulin and guanosine triphosphate regulate dephosphorylation of the beta-subunit of the insulin receptor in sarcolemma membranes isolated from skeletal muscle. 352 89

"Heavy" sarcoplasmic reticulum vesicles loaded with 5 mM CaCl2 in the presence of protease inhibitors were phosphorylated by addition of MgATP in the presence or absence of calmodulin. The major site of phosphorylation was a 60-kDa protein. In the absence of added calmodulin, phosphorylation of the 60-kDa protein reached its maximal value (8 pmol of P/mg of membrane protein) at 1 min. In the presence of 1 microM calmodulin, a 2-fold higher level of phosphorylation (16.1 pmol of P/mg of sarcoplasmic reticulum) was reached within a shorter time (10 s). The phosphoprotein was then spontaneously dephosphorylated. The initial rate of Ca2+ release, which was induced by a Ca2+ jump and determined by stopped-flow fluorometry using chlorotetracycline, decreased upon phosphorylation, whereas it was restored upon dephosphorylation. There was good correlation between the amount of P incorporation into the 60-kDa protein and the extent of inhibition of Ca2+ release. In the presence of added calmodulin the protein kinase activity sharply increased in the [Ca2+] range of 0.2-2 microM with a concentration for half-maximal activation at 0.6 microM. On the other hand, the protein phosphatase activity was virtually independent of calmodulin and [Ca2+] in the [Ca2+] range in which protein kinase was activated. The results suggest that the calmodulin-dependent phosphorylation of the 60-kDa protein plays an important role in the regulation of Ca2+ release from sarcoplasmic reticulum.
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PMID:Involvement of 60-kilodalton phosphoprotein in the regulation of calcium release from skeletal muscle sarcoplasmic reticulum. 374 63

Adenosine 3':5'-monophosphate (cyclic AMP) caused a decrease in the net rate of incorporation of radioactive phosphate into a specific protein (protein D) in a membrane fraction from toad bladder. Moreover, when the membrane protein was prelabeled with radioactive phosphate, cyclic AMP caused an increase in the net rate of removal of radioactive phosphate from this specific protein. Certain agents were shown to be selective inhibitors of membrane-bound protein D kinase or protein D phosphatase. With the help of these agents, it was concluded that cyclic AMP caused the activation of membrane-bound protein D phosphatase. The present data, together with earlier studies, are compatible with the possibility that the cyclic AMP-induced activation of a membrane-bound phosphoprotein phosphatase in toad bladder, with the consequent dephosphorylation of protein D, may be responsible for the physiological effects of antidiuretic hormone on sodium and/or water transport in this tissue.
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PMID:Activation by adenosine 3':5'-monophosphate of a membrane-bound phosphoprotein phosphatase from toad bladder. 435 57

The alkali-labile P content of membrane protein prepared from rapidly frozen rat brain was measured, CuSO(4) being used to inhibit protein phosphatase activity during subcellular fractionation. The P content of the membrane fraction was significantly increased (+12%) over the control value by incubation of homogenates with ATP before fractionation. This suggests that the membrane protein in rat brain is normally only partially phosphorylated.
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PMID:The state of phosphorylation in vivo of membrane-bound phosphoproteins in rat brain. 472 82

In intact red cells a CaMg-ATPase activity commensurable with that of the Ca-pump exists consisting mainly of protein kinase-protein phosphatase enzymes. The Ca:ATP stoichiometry of the Ca-pump is most probably 2:1, the deviation from this value at low [Ca] in inside-out-vesicles is possibly an artifact. Ca-affinity of the Ca-pump is low in intact red cells, where both calmodulin and calmodulin binding protein are present, and the cAMP-dependent activatory mechanism found in many other cells is inactive. Ca-affinity, however, can be enhanced by A23187, by Ca-EGTA buffers at the internal membrane surface (eliminating some structural divalent cations?), by enrichment in calmodulin and loss in calmodulin binding protein and by mild proteolytic effects on the inner surface of the membrane. Mild trypsin treatment of the external surface of the membrane increases the hydrolysis rate, but not the Ca-affinity of the Ca-pump and other CaMg-ATPases, increases membrane protein phosphorylation and protects against echinocytic shape transformation. All these findings reflect the interrelatedness of several membrane components influencing the rate and/or Ca-affinity of CaMg-ATPases.
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PMID:Ca-transport and CaMg-ATPase activity in human red cell preparations. 611 87


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